Figure 4

Hypothetical model for the mode of action of itraconazole against Paracoccidioides . The up-regulation of transcripts such as hormone-sensitive lipase, ADH, IVD and ACO from different metabolic pathways would produce acetyl CoA that would be used for ergosterol synthesis by ERG enzymes. Acetyl CoA would produce phospholipids for the membrane by the action of DGAT and PHS. The induction of BADH and CYSD would lead to production of thiamine, a cofactor of PDH, which would also produce acetyl CoA. GST would conjugate glutathione to xenobiotics and would remove itraconazole from the cell using transporters, allowing for detoxification.